The basic aim of our project is to investigate the biochemistry of the ovarian steroidal hormones regulating the hypothalamic-ovarian axis (particularly progesterone and its 5 alpha-reduced metabolites - 5 alpha-dihydroprogesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one). We hope to elucidate some of the biochemical regulatory mechanisms involved in these steroid feedbacks at neural pituitary levels. The information gained is expected to give new insights into the steroidal regulatory mechanism(s) affecting the hypothalamic-ovarian axis, which may ultimately reveal new avenues for fertility regulation. This past year and presently our group has explored such aspects as: 1) Characteristics of the two enzymes involved in hypothalamic and pituitary progesterone metabolism and in regulating 5 alpha-dihydroprogesterone levels in these tissues (progesterone 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase); 2) Continuation of our studies on the nature, characteristics and components of the in vivo uptake and accumulation of progesterone, 5 alpha-dihydroprogesterone, related steroids and their metabolites by neuroendocrine tissues; 3) The biological role of these 5 alpha-reduced metabolites and their relevancy as intermediaries of progesterone's neuroendocrine effects and their sites of action; 4) The mechanisms, intermediaries and subcellular components involved in the in vitro effects of the sex steroids (particularly progesterone, its 5 alpha-reduced metabolites, estradiol and combinations) on the synthesis, storage and release of leuteinizing hormone releasing factor (LRF) from rat hypothalamus. The above studies should provide further insight and the bases for subsequent experiments to elucidate the sequential scheme of molecular events from sex steroid feedback at neural and pituitary levels to the ultimate release or inhibition of release of the gonadotropins. BIBLIOGRAPHIC REFERENCES: Hanukoglu, I., H.J. Karavolas, and R.W. Goy, 1977. Progesterone metabolism in the pineal, brain stem, thalamus and corpus callosum of the female rat. Brain Res. (In press). Nuti, K.M., and H.J. Karavolas, 1977. Effect of progesterone and its 5 alpha-reduced metabolites on gonadotropin levels in estrogen-primed ovariectomized rats. Endocrinology (In presss-March).